This paper presents an experimental program aimed at assessing the effect of vertical earthquake ground motion on reinforced concrete bridge piers. The program comprised testing of four large scale piers by utilizing the Multi-Axial Full-Scale Sub-Structured Testing and Simulation (MUST-SIM) facility at the University of Illinois. Two hybrid analytical-experimental simulations were used to experimentally investigate the effects of vertical ground motion on pier loading and behavior. Two additional cyclic tests were conducted to allow direct comparison of pier response under tension to pier response under compression. Detail aspects of the experimental framework including a substructuring scheme, analytical representation of structure, test specimen design and advanced measurement system are provided. The observations and interpretation of experimental results, including the impact on both global and local behavior, are discussed. It is concluded that vertical ground motion can significantly impact Reinforced Concrete (RC) pier behavior and failure mode.